The objective of this research is to determine the mechanism by which peptide hormones (such as insulin) stimulate active or passive cation transport across the plasma membrane and secondly to determine whether regulation of cation transport plays an essential role in altering cellular metabolism or differentiation. Two different approaches will be taken toward solving these problems. In the first case, we will obtain a well defined subcellular system which shows insulin regulation of an enzymatic reaction. In particular we will: 1) Attempt to verify insulin inhibition of Ca2 ion-ATPase activity of hepatocyte plasma membranes, 2) Attempt to verify stimulation of mitochondrial pyruvate dehydrogenase by addition of insulin plus fat cell plasma membranes, 3) Determine the minimum requirements of these two systems and use these sub-cellular systems to purify and identify any essential proteins and/or small molecules, 4) Reconstitute plasma membrane vesicles capable of insulin regulated Ca2 ion transport. The second part of this research will be concerned with determining whether an alteration in cation transport is an early and essential event for induction of murine erythroleukemia cells to differentiate into red cells. We intend to test the hypothesis that inducing agents (such as DMSO) act by causing a transient dissipation of the plasma membrane Na ion gradient and/or membrane potential to allow increases in cytoplasmic Ca2 ion concentrations which are essential for later events in differentiation.